The overall objective of this research project is to investigate the physiological mechanisms responsible for autoregulation of renal blood flow, glomerular filtration rate, and peritubular capillary dynamics. At present we do not have an adequate scientific explanation of even the fundamental intrinsic mechanism by which renal vascular resistance is controlled. In fact, even the way in which the renal autoregulatory system affects sodium and water excretion is not well understood. One aspect of this project is to study the interrelationships between the factors that control renal hemodynamics and those that control sodium and water excretion. Emphasis is placed on a "systems analysis" approach to these problems. The specific objectives of this project include: 1) Investigation of the intrinsic feedback system involved in renal autoregulation with further evaluation of the macula densa feedback hypothesis. 2) Study of the transient and steady-state effects of changes in plasma osmolality and plasma colloid osmotic pressure. 3) Investigation of the changes in peritubular capillary dynamics following changes in arterial pressure and plasma colloid osmotic pressure. 4) Investigation of the mechanism of "pressure diuresis" in preparations that exhibit normal autoregulatory behavior. 1) Analysis of the flow, pressure, and resistance characteristics of the renal vascular and tubular networks, as affected by vasoactive substances. 6) Formulation of a unified and concise mathematical model of renal hemodynamics. Methodology to be employed includes a combination of electromagnetic flowmeter studies, tubular transit time measurements, micropressure measurements of tubular and peritubular capillary pressures, measurement of the renal interstitial fluid pressure by the use of the implanted capsule technique and the subcapsular catheter method, clearance techniques and computer simulation studies.